Research Report
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World J Gastroenterol. Nov 14, 2014; 20(42): 15727-15735
Published online Nov 14, 2014. doi: 10.3748/wjg.v20.i42.15727
GW4064, a farnesoid X receptor agonist, upregulates adipokine expression in preadipocytes and HepG2 cells
Xiao-Min Xin, Mu-Xiao Zhong, Gong-Li Yang, Yao Peng, Ya-Li Zhang, Wei Zhu
Xiao-Min Xin, Mu-Xiao Zhong, Gong-Li Yang, Yao Peng, Ya-Li Zhang, Wei Zhu, Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
Xiao-Min Xin, Department of Gastroenterology, Anyang People’s Hospital, Anyang 455000, Henan Province, China
Gong-Li Yang, Department of Gastroenterology, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, China
Author contributions: Xin XM, Zhong MX and Yang GL contributed equally to this work; Xin XM, Zhu W and Zhang YL designed the research; Xin XM, Zhong MX, Yang GL and Peng Y performed the research; Xin XM, Zhu W and Zhang YL analyzed the data; and Xin XM, Zhong MX and Yang GL wrote the paper.
Supported by Guangdong Provincial Science and Technology Projects, No. 2011B050400009; and Scientific Research Projects of Hubei Province Education Department, No. B2014055
Correspondence to: Wei Zhu, PhD, Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, 1838 Guangzhou North Avenue, Baiyun District, Guangzhou 510515, Guangdong Province, China. chnz_w@126.com
Telephone: +86-20-61641533 Fax: +86-20-87280770
Received: March 14, 2014
Revised: June 13, 2014
Accepted: July 11, 2014
Published online: November 14, 2014
Abstract

AIM: To investigate the effect of GW4064 on the expression of adipokines and their receptors during differentiation of 3T3-L1 preadipocytes and in HepG2 cells.

METHODS: The mRNA expression of farnesoid X receptor (FXR), peroxisome proliferator-activated receptor-gamma 2 (PPAR-γ2), adiponectin, leptin, resistin, adiponectin receptor 1 (AdipoR1), adiponectin receptor 2 (AdipoR2), and the long isoform of leptin receptor (OB-Rb) and protein levels of adiponectin, leptin, and resistin were determined using fluorescent real-time PCR and enzyme linked immunosorbent assay, respectively, on days 0, 2, 4, 6, and 8 during the differentiation of 3T3-L1 preadipocytes exposed to GW4064. Moreover, mRNA expression of AdipoR2 and OB-Rb was also examined using fluorescent real-time PCR at 0, 12, 24, and 48 h in HepG2 cells treated with GW4064.

RESULTS: The mRNA expression of FXR, PPAR-γ2, adiponectin, leptin, resistin, AdipoR1, AdipoR2, and OB-Rb and protein levels of adiponectin, leptin, and resistin increased along with differentiation of 3T3-L1 preadipocytes (P < 0.05 for all). The mRNA expression of FXR, PPAR-γ2, adiponectin, leptin, and AdipoR2 in 3T3-L1 preadipocytes, and AdipoR2 and OB-Rb in HepG2 cells was significantly increased after treatment with GW4064, when compared with the control group (P < 0.05 for all). A similar trend was observed for protein levels of adipokines (including adiponectin, leptin and resistin). However, the expression of resistin, AdipoR1, and OB-Rb in 3T3-L1 cells did not change after treatment with GW4064.

CONCLUSION: The FXR agonist through regulating, at least partially, the expression of adipokines and their receptors could offer an innovative way for counteracting the progress of metabolic diseases such as nonalcoholic fatty liver disease.

Keywords: Farnesoid X receptor, Adipokines, Adipokine receptors, 3T3-L1 cells, HepG2 cells, Nonalcoholic fatty liver disease

Core tip: Our study emphasizes for the first time the effect of GW4064, a synthetic farnesoid X receptor (FXR) agonist, on the expression of adipokines and their receptors, and indicates that the way FXR agonist may act in the progress of nonalcoholic fatty liver disease (NAFLD) is at least partially through regulating the expression of adipokines and their receptors. Therefore, our data provide a further theoretical basis for using an FXR agonist in the therapeutic approach of NAFLD.